P53 overexpression represses androgen-mediated induction of NKX3.1 in a prostate cancer cell line

Anli Jiang,Pengju Zhang,Xiaoyan Hu,Weiwen Chen,Chunxiao Yu,Wenwen Liu,Jianye Zhang

doi:10.1038/emm.2006.74

Anli Jiang, Pengju Zhang + Show 5 more

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https://doi.org/10.1038/emm.2006.74

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Journal: Experimental & Molecular Medicine	Publication Date: Dec 1, 2006
Citations: 5	License type: cc-by

Affiliation: Shandong University

Abstract

Prostate cancer is a disease involving complicated multiple-gene alterations. Both NKX3.1 and p53 are related to prostate cancer and play crucial roles in prostate cancer progression. However, little is known about the relationships and interactions between p53 and NKX3.1 in prostate cancer. We found that NKX3.1 expression is down-regulated by over-expression of wild type (wt) p53 in prostate cancer LNCaP cells. NKX3.1 is down-regulated at both the mRNA and protein levels by p53 over- expression due to either transient transfection of exogenous p53 or induction of endogenous p53. p53 over-expression represses androgen-induced transactivation of NKX3.1 by inhibiting the promoter of the androgen acceptor (AR) gene and by blocking AR-DNA binding activity. In addition, transfection with the p21 expression vector (pPSA-p21) showed that p21 does not reduce NKX3.1 expression, indicating that NKX3.1 expression is not the result of nonspecific effects of cell growth arrest. Our results provide biochemical and cellular biologic evidence that NKX3.1 is down-regulated by p53 over-expression in prostate cancer cells.

Highlights

NKX3.1 is an androgen regulated prostate-specific homeobox gene (Prescott et al, 1998) that is thought to be involved in prostate development and carcinogenesis (Bhatia-Gaur et al, 1999)
We report that NKX3.1 expression is regulated by over-expression of wild type p53 in prostate cancer LNCaP cells and we provide evidence for the mechanisms that control down regulation of NKX3.1 by p53 over-expression in
Construction of luciferase reporter plasmids To observe the effects of p53 on NKX3.1 promoter activity,we constructed the pGL3-1040 bp NKX3.1 promoter and its internal deletion mutant of a potential p53 response element (p53 RE)

Summary

Introduction

NKX3.1 is an androgen regulated prostate-specific homeobox gene (Prescott et al, 1998) that is thought to be involved in prostate development and carcinogenesis (Bhatia-Gaur et al, 1999). Loss of NKX3.1 expression has been shown to be associated with hormone-refractory prostate cancer and advanced tumor stage (Bowen et al, 2000); overexpression of NKX3.1 in prostate cancer has been reported (Xu et al, 2000). Cronauer et al analyzed the effect of p53 on androgen signaling in 22Rv1 and LNCaP prostate cancer cells. We report that NKX3.1 expression is regulated by over-expression of wild type (wt) p53 in prostate cancer LNCaP cells and we provide evidence for the mechanisms that control down regulation of NKX3.1 by p53 over-expression in.

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